title: Somatic coding mutations in human induced pluripotent stem cells.
abstract: Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.
authors.affiliation: Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Athurva
authors.initials: A
authors.lastname: Gore
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Ho-Lim
authors.initials: HL
authors.lastname: Fung
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Young
authors.forename: Suneet
authors.initials: S
authors.lastname: Agarwal
authors.forename: Jessica
authors.initials: J
authors.lastname: Antosiewicz-Bourget
authors.forename: Isabel
authors.initials: I
authors.lastname: Canto
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giorgetti
authors.forename: Mason A
authors.initials: MA
authors.lastname: Israel
authors.forename: Evangelos
authors.initials: E
authors.lastname: Kiskinis
authors.forename: Je-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Yuin-Han
authors.initials: YH
authors.lastname: Loh
authors.forename: Philip D
authors.initials: PD
authors.lastname: Manos
authors.forename: Nuria
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authors.lastname: Montserrat
authors.forename: Athanasia D
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authors.lastname: Panopoulos
authors.forename: Sergio
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authors.lastname: Ruiz
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Wilbert
authors.forename: Junying
authors.initials: J
authors.lastname: Yu
authors.forename: Ewen F
authors.initials: EF
authors.lastname: Kirkness
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D004252:DNA Mutational Analysis; D004843:Epistasis, Genetic / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016296:Mutagenesis / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*